Abstract

In non-human primate models of AIDS, attenuated lentiviruses provide the most reliable protection from challenge with pathogenic virus but the extent to which the vaccine virus replicates after challenge is unclear. At 7 and 14 days after vaginal challenge with pathogenic SIVmac239, plasma SIVenv RNA levels were significantly lower in female macaques immunized 6 months earlier with live, attenuated SHIV89.6 compared to unimmunized control animals. In 2 SHIV-immunized, unprotected macaques SIV replication produced moderate-level plasma viremia with dissemination of challenge virus to all tissues on day 14 after challenge. In protected, SHIV-immunized monkeys, SIV replication was controlled in all tissues, from the day of challenge through 14 days post-challenge. Further, in CD8(+) T cell-depleted SHIV-immunized animals, SIV replication and dissemination were more rapid than in control animals. These findings suggest that replication of a pathogenic AIDS virus can be controlled at the site of mucosal inoculation by live-attenuated lentivirus immunization.

Plasma vRNA levels in naive control and SHIV-immunized monkeys monkeys after vaginal challenge with SIVmac239

Plasma SIVgag concentration (copies/ml) at (a) 7 days and (b) 14 days p.c.. Plasma SIVenv concentration (copies/ml) at (c) 7 days and (d) 14 days p.c.. Each symbol represents the result for an individual animal. The horizontal line indicates the mean plasma vRNA level in each animal group. The p values were calculated using a unpaired one-tailed T test.

SIVgag RNA levels in tissues of naïve control and SHIV immunized monkeys after vaginal SIVmac239challenge

(a) naïve control animals (SIVgag RNA copies/μg tissue RNA) and (b) SHIV-immunized animals (SIVgag RNA copies/μg tissue RNA); CD8+ lymphocyte-depleted, SHIV-immunized animals are indicated by a solid horizontal line under the animal numbers at the far right of the x-axis. Anatomic sites are denoted as follows: genital tract (closed red symbols), genital lymph nodes (open red symbols), peripheral lymphoid tissues (closed blue symbols), and intestinal tract/mesenteric LN (green symbols). The vRNA levels for the indicated tissues are displayed vertically above the animal numbers along the x-axis. The animals are grouped by the timing of necropsy after vaginal SIVmac239 challenge, as indicated by the brackets under the animal numbers. The horizontal dotted line indicates the limit of quantification for this assay and represents the cutoff value for designating positive samples.

(a) naïve control animals (SIVenv RNA copies/μg tissue RNA and (b) SHIV-immunized animals (SIVenv RNA copies/μg tissue RNA; CD8+ lymphocyte depleted SHIV-immunized animals are indicated by a solid horizontal line under the animal numbers at the far right of the x-axis. The figure organization is similar to Fig. 2.

(a) SHIV-immunized animals (HIVenv RNA copies/μg tissue RNA; CD8+ lymphocyte-depleted SHIV-immunized animals are indicated by a solid horizontal line under the animal numbers at the far right of the x-axis. The figure organization is similar to Fig. 2.

Comparison of plasma SIVgag concentration (copies/ml) at (a) 7 days and (b) 14 days p.c.; and plasma SIVenv concentration (copies/ml) at (c) 7 days and (d) 14 days p.c. in naïve control and CD8+ T cell-depleted SHIV-immunized animals. Comparison of plasma HIVenv concentration (copies/ml) in SHIV-immunized and CD8+ T cell-depleted, SHIV-immunized animals at (e) 7 days and (f) 14 days p.c.. Each symbol represents the result for an individual animal. The horizontal line indicates the mean plasma vRNA level in each animal group. P values were generated with an unpaired one-tailed T test.